{"title":"基于 TRPV1 离子通道激动剂 RhTx 的多肽抑制剂的设计、合成和功能验证。","authors":"Heng Zhang, Jiawei Wang, Fan Yang","doi":"10.3724/zdxbyxb-2023-0465","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>To design and synthesize peptide inhibitors targeting transient receptor potential vanilloid 1 (TRPV1) ion channel, and to validate their function.</p><p><strong>Methods: </strong>Based on previous studies on the relation of molecular structure and function of red head toxin (RhTx), a series of peptides were rationally designed and synthesized, with positive charged amino acids linked to the N terminus of RhTx. These Nplus-RhTx peptides were functionally validated by patch-clamp recordings in live cells.</p><p><strong>Results: </strong>Among the 8 synthesized Nplus-RhTx peptides, four inhibited TRPV1 ion channel activated by capsaicin with IC<sub>50</sub> of (188.3±4.7), (193.6±18.0), (282.8±11.9) and (299.5±6.4) µmol/L, respectively.</p><p><strong>Conclusions: </strong>It is feasible to develop TRPV1 peptide inhibitors by using rational design based on N terminal residues of RhTx.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11057985/pdf/","citationCount":"0","resultStr":"{\"title\":\"Design, synthesis and functional validation of peptide inhibitors based on TRPV1 ion channel agonist RhTx.\",\"authors\":\"Heng Zhang, Jiawei Wang, Fan Yang\",\"doi\":\"10.3724/zdxbyxb-2023-0465\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>To design and synthesize peptide inhibitors targeting transient receptor potential vanilloid 1 (TRPV1) ion channel, and to validate their function.</p><p><strong>Methods: </strong>Based on previous studies on the relation of molecular structure and function of red head toxin (RhTx), a series of peptides were rationally designed and synthesized, with positive charged amino acids linked to the N terminus of RhTx. These Nplus-RhTx peptides were functionally validated by patch-clamp recordings in live cells.</p><p><strong>Results: </strong>Among the 8 synthesized Nplus-RhTx peptides, four inhibited TRPV1 ion channel activated by capsaicin with IC<sub>50</sub> of (188.3±4.7), (193.6±18.0), (282.8±11.9) and (299.5±6.4) µmol/L, respectively.</p><p><strong>Conclusions: </strong>It is feasible to develop TRPV1 peptide inhibitors by using rational design based on N terminal residues of RhTx.</p>\",\"PeriodicalId\":24007,\"journal\":{\"name\":\"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-04-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11057985/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3724/zdxbyxb-2023-0465\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3724/zdxbyxb-2023-0465","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
Design, synthesis and functional validation of peptide inhibitors based on TRPV1 ion channel agonist RhTx.
Objectives: To design and synthesize peptide inhibitors targeting transient receptor potential vanilloid 1 (TRPV1) ion channel, and to validate their function.
Methods: Based on previous studies on the relation of molecular structure and function of red head toxin (RhTx), a series of peptides were rationally designed and synthesized, with positive charged amino acids linked to the N terminus of RhTx. These Nplus-RhTx peptides were functionally validated by patch-clamp recordings in live cells.
Results: Among the 8 synthesized Nplus-RhTx peptides, four inhibited TRPV1 ion channel activated by capsaicin with IC50 of (188.3±4.7), (193.6±18.0), (282.8±11.9) and (299.5±6.4) µmol/L, respectively.
Conclusions: It is feasible to develop TRPV1 peptide inhibitors by using rational design based on N terminal residues of RhTx.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
